Endoscope Assisted Microvascular Decompression for Trigeminal Neuralgia: Surgical Safety and Efficacy.

BACKGROUND: The cranial nerve (CN) V and adjacent neurovascular structures are crucial landmarks in microvascular decompression (MVD). MVD of CN V is the most effective treatment for patients with drug-resistant trigeminal neuralgia (TN) diagnosis. The endoscope-assisted retrosigmoid approach (RSA) provides better exposure and less cerebellar retraction in the corridor towards the cerebellopontine angle (CPA). METHODS: Five adult cadaver heads (10 sides) underwent dissection of the MVD in park bench position. MVD was simulated using microsurgical RSA, and the anatomical landmarks were defined. Microsurgical dissections were additionally performed along the endoscopic surgical path. Additionally, we present an illustrative case with TN caused by anterior inferior cerebellar artery (AICA) compression. The CN V and its close relationships were demonstrated. Endoscopic and microscopic three-dimensional pictures were obtained. RESULTS: This study increases the anatomical and surgical orientation for CN V and surrounding structures. The CN V arises from the lateral part of the pons and runs obliquely upward toward the petrous apex. It has motor roots that leave from pons antero-supero-medial direction to the sensory root. The endoscopic instruments provide perfect visualization with minimal cerebellar retraction during MVD. CONCLUSION: MVD surgically targets the offending vessel(s) leading to TN and aims to create a disconnected area. The combination of preoperative radiographic assessment with and anatomical correlation provides safe and effective application while facilitating selection of the most appropriate approach. The RSA allows satisfactory visualization for CN V. Endoscope-assisted microsurgery through the CPA is a challenge, it should be performed with advanced anatomical knowledge.

Emerging Roles of Exosomes in Stroke Therapy.

Stroke is the number one cause of morbidity in the United States and number two cause of death worldwide. There is a critical unmet medical need for more effective treatments of ischemic stroke, and this need is increasing with the shift in demographics to an older population. Recently, several studies have reported the therapeutic potential of stem cell-derived exosomes as new candidates for cell-free treatment in stoke. This review focuses on the use of stem cell-derived exosomes as a potential treatment tool for stroke patients. Therapy using exosomes can have a clear clinical advantage over stem cell transplantation in terms of safety, cost, and convenience, as well as reducing bench-to-bed latency due to fewer regulatory milestones. In this review article, we focus on (1) the therapeutic potential of exosomes in stroke treatment, (2) the optimization process of upstream and downstream production, and (3) preclinical application in a stroke animal model. Finally, we discuss the limitations and challenges faced by exosome therapy in future clinical applications.

Biology and Hemodynamics of Aneurysm Rupture.

Predicting rupture risk in intracranial aneurysms is among one of the most critical questions in vascular surgery. The processes that govern an aneurysm growth are multifaceted and complex, but may be summarized into three components: hemodynamics, biology, and mechanics. We review and connect the literature in the three disciplines, identifying considerable strides in recent history and current gaps in research. Taken together, the findings from each field elucidate how and why certain aneurysms rupture, whereas others remain stable. These parameters could eventually inform a translatable predictive model that optimizes risk evaluation and physician's decision-making in treatment options for aneurysms.

Identifying symptomatic trigeminal nerves from MRI in a cohort of trigeminal neuralgia patients using radiomics.

INTRODUCTION: Trigeminal neuralgia (TN) is a devastating neuropathic condition. This work tests whether radiomics features derived from MRI of the trigeminal nerve can distinguish between TN-afflicted and pain-free nerves. METHODS: 3D T1- and T2-weighted 1.5-Tesla MRI volumes were retrospectively acquired for patients undergoing stereotactic radiosurgery to treat TN. A convolutional U-net deep learning network was used to segment the trigeminal nerves from the pons to the ganglion. A total of 216 radiomics features consisting of image texture, shape, and intensity were extracted from each nerve. Within a cross-validation scheme, a random forest feature selection method was used, and a shallow neural network was trained using the selected variables to differentiate between TN-affected and non-affected nerves. Average performance over the validation sets was measured to estimate generalizability. RESULTS: A total of 134 patients (i.e., 268 nerves) were included. The top 16 performing features extracted from the masks were selected for the predictive model. The average validation accuracy was 78%. The validation AUC of the model was 0.83, and sensitivity and specificity were 0.82 and 0.76, respectively. CONCLUSION: Overall, this work suggests that radiomics features from MR imaging of the trigeminal nerves correlate with the presence of pain from TN.

Microglia and Macrophages in Neuroprotection, Neurogenesis, and Emerging Therapies for Stroke.

Stroke remains the number one cause of morbidity in the United States. Within weeks to months after an ischemic event, there is a resolution of inflammation and evidence of neurogenesis; however, years following a stroke, there is evidence of chronic inflammation in the central nervous system, possibly by the persistence of an autoimmune response to brain antigens as a result of ischemia. The mechanisms underlying the involvement of macrophage and microglial activation after stroke are widely acknowledged as having a role in ischemic stroke pathology; thus, modulating inflammation and neurological recovery is a hopeful strategy for treating the long-term outcomes after ischemic injury. Current treatments fail to provide neuroprotective or neurorestorative benefits after stroke; therefore, to ameliorate brain injury-induced deficits, therapies must alter both the initial response to injury and the subsequent inflammatory process. This review will address differences in macrophage and microglia nomenclature and summarize recent work in elucidating the mechanisms of macrophage and microglial participation in antigen presentation, neuroprotection, angiogenesis, neurogenesis, synaptic remodeling, and immune modulating strategies for treating the long-term outcomes after ischemic injury.

Minimally-invasive tubular retraction ports for intracranial neurosurgery: History and future perspectives.

Brain retraction is a necessary yet potentially damaging requirement of accessing lesions located in deep structures. The development of minimally-invasive tubular retractors (MITRs) provides the theoretical advantage of maximizing visualization of and access to deep-seated lesions, all while minimizing collateral tissue damage. These advantages make MITRs preferable to traditional bladed retractors in the majority of deep-seated lesions. Several commercially-available MITR systems currently exist and have been shown to aid in achieving excellent outcomes with acceptable safety profiles. Nevertheless, important drawbacks to currently-available MITR systems exist. Continued pursuit of an ideal MITR system that provides maximal visualization and access to deep-seated lesions while minimizing retraction-related tissue damage is therefore important. In this review, we discuss the historical development of MITRs, the advantages of MITRs compared to traditional bladed retractors, and opportunities to improve the development of prospective MITRs.

Microsurgical Management of the Middle Cerebral Artery Bifurcation Aneurysms: An Anatomic Feasibility Study.

BACKGROUND: The proper head positioning decreases the surgical complications by enabling a better surgical maneuverability. Middle cerebral artery (MCA) bifurcation aneurysms have been classified by Dashti et al. [Surg Neurol. 2007 May;67(5):441-56] as the intertruncal, inferior, lateral, insular, and complex types based on dome projection. Our aim was to identify the optimum head positions and to explain the anatomic variables, which may affect the surgical strategy of MCA bifurcation aneurysms. METHODS: The lateral supraorbital approach bilaterally was performed in the 4 cadaveric heads. All steps of the dissection were recorded using digital camera. RESULTS: The distal Sylvian fissure (SF) dissection may be preferred for insular type and the proximal SF dissection may be preferred for all other types. Fifteen degrees head rotation was found as the most suitable position for the intertruncal, lateral type and subtype of complex aneurysms related with superior trunk. Thirty degrees head rotation was found the most suitable position for the inferior type, insular type, and subtype of complex aneurysms related with inferior trunk. CONCLUSIONS: The head positioning in middle cerebral bifurcation aneurysms surgery is a critical step. It should be tailored according to the projection and its relationship with the parent vessels of the middle cerebral bifurcation.

Neurosurgical management of aneurysms of the vertebrobasilar system: increasing indications for endovascular therapy with a continued role for open microneurosurgery.

Aneurysms of the vertebrobasilar system remain among the most challenging subsets of aneurysms to treat with an open surgical approach. Since Charles Drake's pioneering work in the 1960s, several advances in microsurgical techniques have improved outcomes and feasibility in the open surgical management of these aneurysms. In parallel, the field of endovascular neurosurgery has provided several safe and effective treatment options. Multiple trials have suggested that endovascular therapy for aneurysms of the vertebrobasilar system is superior to open surgical management in most cases. In some instances, however, open surgical management likely represents a more effective and durable option relative to endovascular therapy. Therefore, continued training of future cerebrovascular specialists in open surgery of vertebrobasilar aneurysms remains crucial. With widespread utilization of endovascular techniques, however, proper exposure of trainees to such aneurysms is growing increasingly difficult. In this review, we discuss the recent advances in the endovascular management of vertebrobasilar aneurysms while also emphasizing the continued importance of open microneurosurgery in such cases.

The Rate of Symptomatic Ischemic Events after Passing Balloon Test Occlusion of the Major Intracranial Arteries: Meta-Analysis.

BACKGROUND: Balloon test occlusion is a widely used method for predicting tolerance of vessel occlusion in the treatment of aneurysms, fistulae, and head and neck neoplasms. However, the false-negative rate is variably reported due in part to the diversity of perfusion monitoring methods. OBJECTIVE: To evaluate the rate of symptomatic ischemic events after a negative balloon test occlusion and determine whether perfusion monitoring methods contribute to differences in these rates. METHODS: PubMed was systematically searched for studies between 1990 and 2020 that reported rates of ischemic outcomes of parental vessel occlusion in patients who passed balloon test occlusion. A generalized linear mixed model meta-analysis was performed. Results were expressed as the rate of symptomatic ischemic events after parental vessel occlusion without vessel bypass in patients who passed balloon test occlusion. RESULTS: Thirty-two studies met the inclusion criteria. The overall pooled rate of ischemic events after passing balloon test occlusion was 3.7% (95% confidence interval [CI]: 1.7-7.8). This rate was 3.8% (95% CI: 1.1-12.8) when monitored with angiography, 2.2% (95% CI: 0.4-10.2) when monitored by a form of computed tomography, and 5.3% (95% CI: 1.2-20.4) when monitored by 2 or more methods of perfusion assessment. The complication rate of balloon test occlusion was 0.8% (95% CI: 0.2-2.7). CONCLUSIONS: Balloon test occlusion results in a low rate of subsequent ischemic events, without conclusive evidence of variation between methods of perfusion assessment. The choice of method should focus on reduction of complication risk, experience of the interventional team, and avoidance of prolonged test occlusion times.

Zika virus-based immunotherapy enhances long-term survival of rodents with brain tumors through upregulation of memory T-cells.

Zika virus (ZIKV) exhibits a tropism for brain tumor cells and has been used as an oncolytic virus to target brain tumors in mice with modest effects on extending median survival. Recent studies have highlighted the potential for combining virotherapy and immunotherapy to target cancer. We postulated that ZIKV could be used as an adjuvant to enhance the long-term survival of mice with malignant glioblastoma and generate memory T-cells capable of providing long-term immunity against cancer remission. To test this hypothesis mice bearing malignant intracranial GL261 tumors were subcutaneously vaccinated with irradiated GL261 cells previously infected with the ZIKV. Mice also received intracranial injections of live ZIKV, irradiation attenuated ZIKV, or irradiated GL261 cells previously infected with ZIKV. Long-term survivors were rechallenged with a second intracranial tumor to examine their immune response and look for the establishment of protective memory T-cells. Mice with subcutaneous vaccination plus intracranial irradiation attenuated ZIKV or intracranial irradiated GL261 cells previously infected with ZIKV exhibited the greatest extensions to overall survival. Flow cytometry analysis of immune cells within the brains of long-term surviving mice after tumor rechallenge revealed an increase in the number of T-cells, including CD4+ and tissue-resident effector/ effector memory CD4+ T-cells, in comparison to long-term survivors that were mock-rechallenged, and in comparison to naïve untreated mice challenged with intracranial gliomas. These results suggest that ZIKV can serve as an adjuvant to subcutaneous tumor vaccines that enhance long-term survival and generate protective tissue-resident memory CD4+ T-cells.

From the Historical Examples of Drs. Osler, Cushing, and Van Wagenen: Lessons on the Importance of Mentorship in Contemporary Neurosurgery.

Although the historical relationships between William Osler, Harvey Williams Cushing, and William Perine Van Wagenen are well known in the neurosurgical world, the nature of the mentor-mentee relationships that existed between these historical giants is not widely appreciated. In this historical vignette, we describe and exemplify such relationships, while at the same time extract important and applicable principles from them. We reviewed relevant primary and secondary sources that documented the interactions between Cushing, Osler, and Van Wagenen. In founding the field of neurological surgery, the brilliant yet volatile Dr. Harvey Cushing received guidance from his mentor, Dr. William Osler. Through our review, it is undeniable that Dr. Osler's personal and professional guidance was vital to young Dr. Cushing's success as the founder of modern neurosurgery. Likewise, Cushing's tutelage of Van Wagenen enabled Van Wagenen to become a leader of a second generation of neurosurgeons, thereby perpetuating the existence of Cushing's high neurosurgical standards. These historical mentor-mentee relationships were built on 4 primary components: accurate recognition of talent, guidance, arrangement of opportunity, and sustenance of mentorship-actions that are commonly implicated in effective mentorship in contemporary studies. Proper mentorship remains indispensable for the success of neurosurgical trainees.

Efficacy of stem cell-based therapies for stroke.

Stroke remains a prevalent disease with limited treatment options. Available treatments offer little in the way of enhancing neurogenesis and recovery. Because of the limitations of available treatments, new therapies for stroke are needed. Stem cell-based therapies for stroke offer promise because of their potential to provide neurorestorative benefits. Stem cell-based therapies aim to promote neurogenesis and replacement of lost neurons or protect surviving neurons in order to improve neurological recovery. The mechanism through which stem cell treatments mediate their therapeutic effect is largely dependent on the type of stem cell and route of administration. Neural stem cells have been shown in pre-clinical and clinical trials to promote functional recovery when used in intracerebral transplantations. The therapeutic effects of neural stem cells have been attributed to their formation of new neurons and promotion of neuroregeneration. Bone marrow stem cells (BMSC) and mesenchymal stem cells (MSC) have been shown to enhance neurogenesis in pre-clinical models in intracerebral transplantations, but lack clinical evidence to support this therapeutic approach in patients and appear to be less effective than neural stem cells. Intravenous and intra-arterial administration of BMSC and MSC have shown more promise, where their effects are largely mediated through neuroprotective mechanisms. The immune system has been implicated in exacerbating initial damage caused by stroke, and BMSC and MSC have demonstrated immunomodulatory properties capable of dampening post-stroke inflammation and potentially improving recovery. While still in development, stem cell therapies may yield new treatments for stroke which can improve neurological recovery.

Interspecies Organogenesis for Human Transplantation.

Blastocyst complementation combined with gene editing is an emerging approach in the field of regenerative medicine that could potentially solve the worldwide problem of organ shortages for transplantation. In theory, blastocyst complementation can generate fully functional human organs or tissues, grown within genetically engineered livestock animals. Targeted deletion of a specific gene(s) using gene editing to cause deficiencies in organ development can open a niche for human stem cells to occupy, thus generating human tissues. Within this review, we will focus on the pancreas, liver, heart, kidney, lung, and skeletal muscle, as well as cells of the immune and nervous systems. Within each of these organ systems, we identify and discuss (i) the common causes of organ failure; (ii) the current state of regenerative therapies; and (iii) the candidate genes to knockout and enable specific exogenous organ development via the use of blastocyst complementation. We also highlight some of the current barriers limiting the success of blastocyst complementation.

Neural Repair in Stroke.

This article reviews the progress that has been made in the development of cell therapies for the repair of nervous system damage caused by strokes, since the first report on the use of cell transplants in animal models of ischemic brain injury in 1988. At that time neural progenitor cells derived from fetal brain tissue were used as sources of cells to replace specific subsets of neuronal cells that were lost in various regions of the brain following experimentally induced strokes. Since 1988, cells from other sources, such as embryonic stem cells and inducible pluripotent stem cells, have been investigated for their ability to replace neuronal cells and repair the damaged brain. Most recently, mesenchymal stem cells and cord blood stem cells have been studied for the ability to modulate the immune system and ameliorate the neuropathology and neurological deficits associated with experimental stroke. The preclinical investigation of different cell therapy approaches for treating stroke during the past three decades has now led to many ongoing clinical trials, with the clinical evaluation of stem cell therapies for stroke now involving global participants.

Immunomodulation with Human Umbilical Cord Blood Stem Cells Ameliorates Ischemic Brain Injury - A Brain Transcriptome Profiling Analysis.

Our group previously demonstrated that administration of a CD34-negative fraction of human non- hematopoietic umbilical cord blood stem cells (UCBSC) 48 h after ischemic injury could reduce infarct volume by 50% as well as significantly ameliorate neurological deficits. In the present study, we explored possible mechanisms of action using next generation RNA sequencing to analyze the brain transcriptome profiles in rats with ischemic brain injury following UCBSC therapy. Two days after ischemic injury, rats were treated with UCBSC. Five days after administration, total brain mRNA was then extracted for RNAseq analysis using Illumina Hiseq 2000. We found 275 genes that were significantly differentially expressed after ischemic injury compared with control brains. Following UCBSC treatment, 220 of the 275 differentially expressed genes returned to normal levels. Detailed analysis of these altered transcripts revealed that the vast majority were associated with activation of the immune system following cerebral ischemia which were normalized following UCBSC therapy. Major alterations in gene expression profiles after ischemia include blood-brain-barrier breakdown, cytokine production, and immune cell infiltration. These results suggest that UCBSC protect the brain following ischemic injury by down regulating the aberrant activation of innate and adaptive immune responses.

Anterior temporal artery to posterior cerebral artery bypass for revascularization of the posterior circulation: An anatomical study.

We describe a novel intracranial-to-intracranial bypass technique between the anterior temporal artery and the posterior cerebral artery for revascularization of the posterior circulation. Four formalin-fixed human heads were examined to demonstrate the detailed anatomy of the middle cerebral artery and the posterior cerebral artery, and to illustrate the step-by-step bypass procedure. The anterior temporal artery, a branch of the middle cerebral artery, can be anastomosed to the P2 segment of the posterior cerebral artery as an alternative to extracranial bypass donor segments for treatment of complex aneurysms requiring revascularization. The anastomosis of the anterior temporal artery as a pedicled donor to the posterior cerebral artery provides a shorter graft, due to its close anatomical position to the posterior cerebral artery, for posterior circulation revascularization.

Cortical Bone Trajectory Screw for Lumbar Fixation: A Quantitative Anatomic and Morphometric Evaluation.

BACKGROUND: Lumbar cortical bone trajectory (CBT) screw constructs provide an alternative method of pedicle screw fixation in minimally invasive spine surgery. In this study, we explored the CBT technique in further anatomic detail. The primary aims were to evaluate variations in anatomy relevant to CBT screw placement and to determine optimal screw location, trajectory, and length using measures obtained from computed tomography (CT) scans. METHODS: One hundred CT scans of the lumbar spine were reviewed, and 14 total measurements of entry points, trajectories, and lengths for placement of CBT screws were evaluated. RESULTS: Across all lumbar levels, the mean right pedicle-pars interarticularis junction length ranged from 7.58 ± 1.18 mm to 8.37 ± 1.42 mm, and the mean left pedicle-pars interarticularis junction length ranged from 7.95 ± 1.42 mm to 8.6 ± 1.74 mm. The pedicle-pars interarticularis junction from L1 to L5 was deemed too small for a 5-mm-diameter CBT screw in 35%, 24%, 17%, 17%, and 19%, respectively, on the right, and in 30%, 17%, 17%, 17%, and 20%, respectively, on the left. The average length of a screw placed along the cranial cortical bone of the pedicle ranged from 27 ± 2.5 mm to 30.5 ± 3.4 mm, and the angle of the screw with respect to the vertebral body endplate ranged from 44 ± 4.1° to 48 ± 6.2°. CONCLUSIONS: Improved anatomic knowledge relevant to CBT screw placement for lumbar fixation offers the potential for improving outcomes and reducing complications. Moreover, detailed analysis of the anatomy of the pedicle-pars interarticularis junction via preoperative CT can aid in determining the ideal fixation method.

Isolated Hypertrophic Neuropathy of the Oculomotor Nerve.

BACKGROUND: Hypertrophic neuropathy is a rare entity commonly associated with peripheral nerve, characterized by onion bulb formations. Its cranial nerve involvement is very rare; only 7 cases have been found in the literature. CASE DESCRIPTION: A 32-year-old white man with a 5-year history of intermittent right retro-orbital headache and mild right ptosis presented to the Neurosurgery Clinic. A magnetic resonance imaging of his brain demonstrated an enhancing lesion associated with the right third nerve. He underwent biopsy of the lesion, and its pathology report confirmed the diagnosis of hypertrophic neuropathy. Within 4 months, his third nerve palsy had completely resolved and was functioning fully. CONCLUSIONS: Here, we report a first case of isolated hypertrophic neuropathy involving the oculomotor nerve.

The Lateral Mesencephalic Vein: Surgical Anatomy and Its Role in the Drainage of Tentorial Dural Arteriovenous Fistulae.

BACKGROUND: The lateral mesencephalic vein (LMV) represents an important connection between the infratentorial and supratentorial compartments. It joins the basal vein of Rosenthal and the petrosal system. In our experience with management of tentorial dural arteriovenous fistulas (DAVFs) we have often noted involvement of the lateral mesencephalic vein (LMV) in the venous drainage of these fistulas. METHODS: We reviewed the clinical and angiographic findings of 26 patients with tentorial DAVFs to study the incidence and pattern of drainage through the LMV. In addition, we reviewed the pertinent literature on the anatomy of the LMV. RESULTS: The LMV was involved in the venous drainage of 31% (8/26) of patients with tentorial DAVFs. The direction of venous drainage through the LMV is more commonly from the infratentorial to the supratentorial compartment. There were no specific clinical symptoms/signs associated with tentorial DAVFs involving the LMV compared with those without LMV involvement. When involved in DAVF drainage, the LMV could be invariably identified on noninvasive imaging studies. We present illustrative clinical/angiographic cases and provide a detailed review of the pertinent clinical anatomy of this important but often neglected intracranial vein. CONCLUSIONS: The LMV is a constant venous anastomosis between the supratentorial and infratentorial compartments. Detailed knowledge of the most common variations of the LMV surgical and radiological anatomy has important clinical implications. The vein is an important anatomic landmark during surgery of midbrain lesions. It is often involved in the tentorial DAVF drainage, and it is critical in understanding some "unexpected" venous complications during surgery for posterior fossa lesions.